US3258458A - 9alpha-fluoro-5', 11beta-dihydroxy-4', 5'-dihydro-spiro[androst-4-ene-17, 2'(3'h)-furan]-3-one, corresponding 5'-ethers, and precursor - Google Patents
9alpha-fluoro-5', 11beta-dihydroxy-4', 5'-dihydro-spiro[androst-4-ene-17, 2'(3'h)-furan]-3-one, corresponding 5'-ethers, and precursor Download PDFInfo
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- US3258458A US3258458A US373098A US37309864A US3258458A US 3258458 A US3258458 A US 3258458A US 373098 A US373098 A US 373098A US 37309864 A US37309864 A US 37309864A US 3258458 A US3258458 A US 3258458A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
Definitions
- This invention relates to 9a-fiuoro-5',1lfi-dihydroxy- 4,5-dihydrospiro [androst-4-ene- 17,2 3 'H -furan] -3-one, corresponding 5-ethers, and intermediates thereto. More particularly, this invention provides novel, useful, and unobvious chemical compounds of the formula wherein R represents hydrogen or an alkyl radical and X represents halogen.
- alkyl radicals represented by R especially lower alkyl radicals are preferred, which is to say methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tertbutyl, pentyl, neopentyl, hexyl, isohexyl, heptyl, and like monovalent, saturated, acyclic, straightor branchedchain, hydrocarbon groupings of the formula wherein n repersents a positive integer less than 8.
- halogens represented by X include fluorine, chlorine, and bromine, of which fluorine appears to be best adapted to the purposes hereinafter set forth.
- the compounds to which this invention relates are characterized by valuable pharmacological properties. For exampleand surprisingly-they manifest progestational activity in the well-known Clauberg assay for this effect. They also block the effect to desoxycorticosterone acetate on urinary sodium and potassium.
- Preparation of the subject compounds proceeds by reducing a tetrahydrofuran solution of 3-(3-ethoxy-9a-halo- 1 1B, 17f3-dihydroxyandrosta-3 ,5 -dienl7-yl -propionic acid lactone in liquid ammonia with metallic sodium to the corresponding lactol, which affords the corresponding 4- en-3-one on acidification with hydrochloric acid in dioxane solution and, alternatively, the 5'-ethereal 4-en-3-ones if an alkanol be present during acid treatment.
- the product has the formula EXAMPLE 2 9a fluoro 11,8 hydroxy 5 methoxy 4,5 dillydrospiro[andr0st-4-ene-17,Z(3'H)furan] 3 0ne.
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Description
United States Patent 3,258,458 9a-FLUOR0-5,1lfi-DIHYDROXY 4',5' DIHYDRO- SPIRO[ANDROST 4 ENE 17,2(3H) FURAN1-3- ONE, CORRESPONDING -ETHERS, AND PRE- CURSOR Edward A. Brown, Wilmette, Ill., assignor to G. D. Searle & Co., Chicago, 111., a corporation of Delaware N0 Drawing. Filed June 5, 1964, Ser. No. 373,098
4 Claims. (Cl. 260239.55)
This invention relates to 9a-fiuoro-5',1lfi-dihydroxy- 4,5-dihydrospiro [androst-4-ene- 17,2 3 'H -furan] -3-one, corresponding 5-ethers, and intermediates thereto. More particularly, this invention provides novel, useful, and unobvious chemical compounds of the formula wherein R represents hydrogen or an alkyl radical and X represents halogen.
Among the alkyl radicals represented by R, especially lower alkyl radicals are preferred, which is to say methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tertbutyl, pentyl, neopentyl, hexyl, isohexyl, heptyl, and like monovalent, saturated, acyclic, straightor branchedchain, hydrocarbon groupings of the formula wherein n repersents a positive integer less than 8.
The halogens represented by X include fluorine, chlorine, and bromine, of which fluorine appears to be best adapted to the purposes hereinafter set forth.
The compounds to which this invention relates are characterized by valuable pharmacological properties. For exampleand surprisingly-they manifest progestational activity in the well-known Clauberg assay for this effect. They also block the effect to desoxycorticosterone acetate on urinary sodium and potassium.
Preparation of the subject compounds proceeds by reducing a tetrahydrofuran solution of 3-(3-ethoxy-9a-halo- 1 1B, 17f3-dihydroxyandrosta-3 ,5 -dienl7-yl -propionic acid lactone in liquid ammonia with metallic sodium to the corresponding lactol, which affords the corresponding 4- en-3-one on acidification with hydrochloric acid in dioxane solution and, alternatively, the 5'-ethereal 4-en-3-ones if an alkanol be present during acid treatment.
The following examples describe in detail compounds illustrative of the present invention and methods which have been devised for their preparation. However, the invention is not to be construed as limited thereby, either in spirit or in scope, since it will be apparent to those skilled in the art of organic synthesis that many modifications, both of materials and of methods, may be practiced wtihout departing from the purpose and intent of this disclosure. Throughout the examples hereinafter set forth, temperatures are given in degrees centigrade and relative amounts of materials in parts by weight, except as otherwise noted.
EXAMPLE 1 A. 3 cthoxy 9a fluoro 4',5' dihydrospir0=[androst-4-ene-17,2 (3H)furane] -5',11,8-di0l.-To 300 parts of liquid ammonia is added, with vigorous stirring, at solution of 10 parts of 3-(3-ethoxy-9u-fluoro-l15,17fi-dihydroxyandrosta-3,5-dien-l7a-yl)propionic acid lactone in 450 parts of tetrahydrofuran followed, during 8 minutes, by 5 parts of sodium metal. Stirring is continued for 12 minutes, at which point 6 parts of ethanol is carefully stirred in during 3 minutes. The bulk of the ammonia is then allowed to evaporate, at which point the reaction mixture is poured into 6000 parts of cold water. The precipitate thrown down is filtered off, washed with water, dried in air, and thereupon recrystallized from ethyl acetate to afford 3-ethoxy-9a-fiuoro-4',5'-dihydrospiro [androst-4-ene-17,2'(3H)furane] -5',1 l fl-diol, melting at 166170.
B. 9a fluoro 5',11fl dihydroxy 4',5' dihydrospiro- [andr0st-4-ene-17,2'(3'H)fwran]-3-0ne.To a solution of 30 parts of 3-ethoxy-9ot-fluoro-4,5'-dihydrospiro[androst-4-ene-17,2"(3'H)furane]-5',1lfi-diol in 400 parts of dioxane is added 10 parts of water and 5 parts of concentrated hydrochloric acid. The resultant mixture is allowed to stand at room temperatures for 2 hours, whereupon it is diluted with 2000 parts of water. The precipitate thrown down is filtered olf, washed with water, dried in air, and thereupon recrystallized from-ethyl acetate to give 9a-fluoro-5,11fl-dihydroxy-4',5-dihydrospiro- [androst-4-ene-17,2'(3H)furan]-3-one melting at 221- 226". The product has the formula EXAMPLE 2 9a fluoro 11,8 hydroxy 5 methoxy 4,5 dillydrospiro[andr0st-4-ene-17,Z(3'H)furan] 3 0ne.To a suspension of 25 parts of 3-ethoxy-9a-fluoro-4,5'-dihydrospiro[androst-4-ene-17,2(3'H)furane]-5',11B diol in 400 parts of methanol is added parts of water and 119 parts of concentrated hydrochloric acid. The resultant mixture is stirred at room temperatures for 45 min utes, during which solution, followed by precipitation, occurs. The mixture is chilled to further precipitation. The precipitate is filtered 01f and washed on the filter with a small amount of methanol, whereupon it is dried in air. The product thus isolated is 9a-fluoro-1lfl-hydroxy-5- methoxy-4',5'-dihydrospiro[androst-4 ene 17,2'(3'H)- furan]-3-one melting at 214-219", the formula of which -O CH:
3 What is claimed is: 1. A compound of the formula 4 wherein R is selected from the group consisting of hydrogen and lower alkyl radicals.
2. 9oz fluoro 5,11fi dihydroxy 4',5' dihydrospiro- 5 [androst-4-ene-17,2'(3'H)furan]-3-one.
3. 9oz fluoro 11 3 hydroxy 5 methoxy 4',5- dihydrospiro [androst-4-ene- 17,2 3 'H) furan] -3 -one.
4. 3 -ethoxy 90c fluoro 4',5' dihydrospiro[androst- 0 4-ene-17,2'(3'H)furane]-5',11/3-dio1.
v No references cited.
LEWIS GO'ITS, Primary Examiner.
Claims (1)
1. A COMPOUND OF THE FORMULA
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US373098A US3258458A (en) | 1964-06-05 | 1964-06-05 | 9alpha-fluoro-5', 11beta-dihydroxy-4', 5'-dihydro-spiro[androst-4-ene-17, 2'(3'h)-furan]-3-one, corresponding 5'-ethers, and precursor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US373098A US3258458A (en) | 1964-06-05 | 1964-06-05 | 9alpha-fluoro-5', 11beta-dihydroxy-4', 5'-dihydro-spiro[androst-4-ene-17, 2'(3'h)-furan]-3-one, corresponding 5'-ethers, and precursor |
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| Publication Number | Publication Date |
|---|---|
| US3258458A true US3258458A (en) | 1966-06-28 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US373098A Expired - Lifetime US3258458A (en) | 1964-06-05 | 1964-06-05 | 9alpha-fluoro-5', 11beta-dihydroxy-4', 5'-dihydro-spiro[androst-4-ene-17, 2'(3'h)-furan]-3-one, corresponding 5'-ethers, and precursor |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009083270A1 (en) * | 2007-12-29 | 2009-07-09 | Bayer Schering Pharma Aktiengesellschaft | 15,16-methylene-steroid-17,17-lactol derivative, use thereof, and medicament containing said derivative |
-
1964
- 1964-06-05 US US373098A patent/US3258458A/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| None * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009083270A1 (en) * | 2007-12-29 | 2009-07-09 | Bayer Schering Pharma Aktiengesellschaft | 15,16-methylene-steroid-17,17-lactol derivative, use thereof, and medicament containing said derivative |
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